1,2-Dichloroethane → N-(2-((S)-1-Amino-3-(4-hydroxyphenyl)-1-oxopropan-2-ylamino)-2-oxoethyl)-2-(5-formylthiazol-2-ylamino)-3-methylbutanamide

HRID 1755448Notes

Reaction equation

HRID 1755448 reaction equation
[CH:1]([C:3]1[S:7][C:6]([NH:8][C@@H:9]([CH:13]([CH3:15])[CH3:14])[C:10]([OH:12])=O)=[N:5][CH:4]=1)=[O:2].Cl.[NH2:17][CH2:18][C:19]([NH:21][C@H:22]([C:31]([NH2:33])=[O:32])[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=1)=[O:20].C(Cl)CCl.ON1C2N=CC=CC=2N=N1.CN1CCOCC1.C(O)(C(F)(F)F)=O>CN(C=O)C>[NH2:33][C:31](=[O:32])[C@@H:22]([NH:21][C:19](=[O:20])[CH2:18][NH:17][C:10](=[O:12])[CH:9]([NH:8][C:6]1[S:7][C:3]([CH:1]=[O:2])=[CH:4][N:5]=1)[CH:13]([CH3:15])[CH3:14])[CH2:23][C:24]1[CH:25]=[CH:26][C:27]([OH:30])=[CH:28][CH:29]=1

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 181649HOAtHCID 24212116(2S)-2-[(aminoacetyl)amino]-3-(4-hydroxyphenyl)propanamide hydrochlorideHCID 89858211(S)-2-(5-Formylthiazol-2-ylamino)-3-methylbutanoic acid

Product 1

HCID 86700099N-(2-((S)-1-Amino-3-(4-hydroxyphenyl)-1-oxopropan-2-ylamino)-2-oxoethyl)-2-(5-formylthiazol-2-ylamino)-3-methylbutanamideYield 114.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Following the procedure described in Example 4, except using the material from Example 20 (77 mg, 0.169 mmol), glycyl-L-tyrosinamide hydrochloride (159.5 mg, 0.583 mmol), EDC (190.3 mg, 0.993 mmol), 1-hydroxy-7-azabenzotriazole (29 mg, 0.213 mmol), anhydrous DMF (4 mL) and N-methylmorpholine (350 μL, 3.18 mmol), 86.7 mg (41%) of the title compound is obtained as an orange solid as a TFA salt. Purification is done by preparative HPLC (Condition A) using a PHENOMENEX® Luna Axia 30×100 mm S10 column from 15% Solvent B to 85% Solvent B over 11 min, ret, T=6.82-6.69 min. LC/MS (Condition A): ret. T=2.11-2.18 min, (M+H)+ 448.18.

Sources & evidence

ORD record
ord-6961fb3f9e9c4f1e9d4e1d401a5c852c
Source dataset
uspto-grants-2015_10
Patent number
US09169295B2

Reaction notes

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